Ocular Surface最新文献

Purpose

To evaluate the diagnostic performance of corneal and conjunctival staining, and lid wiper epitheliopathy (LWE) in detecting dry eye disease, as defined by the global consensus Tear Film and Ocular Surface Society Dry Eye Workshop II (TFOS DEWS II) criteria.

Methods

A total of 2066 community residents (1285 females; mean ± SD age, 40 ± 19 years) were recruited in an investigator-masked, prospective registry-based, diagnostic accuracy study. Dry eye symptomology and ocular surface parameters were assessed in a single clinical session. The Sjögren's International Collaborative Clinical Alliance (SICCA) corneal and conjunctival staining scoring and Korb lid wiper epitheliopathy (LWE) grading were evaluated by an independent masked assessor.

Results

Overall, 807 (39 %) participants fulfilled the TFOS DEWS II criteria for dry eye disease, of which 178 (9 %) participants were classified as moderate-to-severe disease. The discriminative abilities of superior and inferior LWE (C-statistics, 0.724 and 0.712, respectively) were greater than corneal and conjunctival staining (C-statistics, 0.573 and 0.627, respectively). The Youden-optimal diagnostic cut-offs for the SICCA corneal and conjunctival staining scores were both ≥1, and the optimal thresholds for the Korb superior and inferior LWE grades were both ≥1. LWE was more commonly detected in both mild-to-moderate and moderate-to-severe dry eye disease, and demonstrated more consistent correlation with other ocular surface parameters across a broader range of disease severity.

Conclusions

LWE demonstrates superior diagnostic performance relative to corneal and conjunctival staining. These findings would support the routine incorporation of LWE evaluation as part of the diagnostic workup of dry eye disease.

Breast cancer is the most prevalent cancer worldwide. With advancements in breast cancer diagnosis and treatment, the prognosis of patients with early-stage cancer has significantly improved. Enhancing the long-term quality of life of patients after antineoplastic therapy, including visual quality, has become a crucial research focus. This review aims to comprehensively summarize dry eye disease adverse reaction resulting from pharmacotherapy for early-stage breast cancer. Through a review of the relevant literature, this study explored the etiology, clinical features, and potential therapeutic strategies for drug-induced dry eye disease in breast cancer treatment. A thorough understanding of the medication-induced dry eye disease adverse reaction aid clinicians in monitoring and managing patients' ocular health more effectively, facilitating early diagnosis and intervention, preventing complications, and ensuring optimal visual protection for patients undergoing breast cancer treatment.

Purpose

To investigate the toxicity of type I interferons (IFNs) on the ocular surface and assess their efficacy in ocular surface tumors.

Methods

We examined the effects of IFN-α2a, IFN-α2b and IFN-β on corneal epithelial cells and stromal fibroblasts in vitro as well as the impact of IFN-α2a on the ocular surface in mice. Additionally, we analyzed the therapeutic and adverse effects of topically administered IFN-α2a and IFN-α2b in patients with ocular surface tumors. Risk factors contributing to side effects were explored.

Results

IFN-α2a, IFN-α2b or IFN-β reduced cell viability and induced pro-inflammatory cytokines in corneal epithelial cells and stromal fibroblasts. Furthermore, IFNs enhanced the expression of major histocompatibility complex class II and CD40 in corneal epithelial cells. In mice, subconjunctival IFN-α2a injection did not induce corneal epithelial defects or opacity, nor did it reduce aqueous tears or conjunctival goblet cells. In patients, topical IFN-α2a or IFN-α2b administration decreased tumor size and prevented recurrence; however, it was associated with mild side effects, including corneal epitheliopathy and conjunctival hyperemia. These complications were associated with longer IFN use, the presence of underlying ocular surface disease and concurrent use of mitomycin C or anti-glaucoma eye drops.

Conclusion

Although type I IFNs cause direct toxicity on corneal cells, they do not induce significant side effects on the healthy ocular surface. Considering its therapeutic and preventive effects, topical type I IFN is safe and effective for treating ocular surface tumors. The potential for ocular side effects should be considered in eyes with identified risk factors.

The Mpox virus (MPXV) is the causative agent of human Mpox disease – a debilitating rash illness similar to smallpox. Although Clade I MPXV has remained endemic to West and Central Africa, Clade II MPXV has been responsible for many outbreaks worldwide. The most recent outbreak in 2022 resulted from the rapid spread of a new clade of MPXV, classified into Clade IIb – a distinct lineage from the previously circulating viral strains. The rapid spread and increased severity of Mpox disease by the Clade IIb strain have raised the serious public health imperative of better understanding the host and viral determinants during MPXV infection. In addition to typical skin rashes, including in the periorbital area, MPXV causes moderate to severe ophthalmic manifestations – most commonly, ocular surface complications (e.g., keratitis, conjunctivitis, blepharitis). While ocular manifestations of Clade I Mpox within the Congo basin have been well-reported, global incidence trends of ocular Mpox cases by Clade IIb are still emerging. Given the demonstrated ability of all MPXV strains to auto-inoculate ocular tissue, alongside the enhanced transmissibility of the Clade IIb virus, there is an urgent need to elucidate the mechanisms by which MPXV causes ocular anomalies. In this review, we discuss the viral and genomic structures of MPXV, the epidemiology, and pathology of systemic and ocular Mpox, as well as potential prophylactic and therapeutic interventions.

Purpose

The lacrimal gland is essential for maintaining ocular surface health and avoiding external damage by secreting an aqueous layer of the tear film. However, a healthy lacrimal gland's inventory of cell types and heterogeneity remains understudied.

Methods

Here, 10X Genome-based single-cell RNA sequencing was used to generate an unbiased classification of cellular diversity in the extraorbital lacrimal gland (ELG) of C57BL/6J mice. From 43,850 high-quality cells, we produced an atlas of cell heterogeneity and defined cell types using classic marker genes. The possible functions of these cells were analyzed through bioinformatics analysis. Additionally, the CellChat was employed for a preliminary analysis of the cell-cell communication network in the ELG.

Results

Over 37 subclasses of cells were identified, including seven types of glandular epithelial cells, three types of fibroblasts, ten types of myeloid-derived immune cells, at least eleven types of lymphoid-derived immune cells, and five types of vascular-associated cell subsets. The cell-cell communication network analysis revealed that fibroblasts and immune cells play a pivotal role in the dense intercellular communication network within the mouse ELG.

Conclusions

This study provides a comprehensive transcriptome atlas and related database of the mouse ELG.

Purpose

Human donor corneas are an essential control tissue for corneal research. We utilized whole mount immunofluorescence (WM-IF) to evaluate how the storage affects the tissue integrity and putative limbal stem cells in human and porcine corneas. Moreover, we compare this information with the marker expression patterns observed in human pluripotent stem cell (hPSC)-derived LSCs.

Methods

The expression of putative LSC markers was analyzed with WM-IF and the fluorescence intensity was quantified in human donor corneas stored for 1–30 days, and in porcine corneas processed 0–6 h after euthanasia. The results were compared with the staining of human and porcine corneal cryosections and with both primary and hPSC-derived LSC cultures.

Results

WM-IF analyses emerged as a more effective method when compared to tissue sections for visualizing the expression of LSC markers within human and porcine corneas. Storage duration was a significant factor influencing the expression of LSC markers, as human tissues stored longer exhibited notable epithelial degeneration and lack of LSC markers. Porcine corneas replicated the expression patterns observed in fresh human tissue. We validated the diverse expression patterns of PAX6 in the limbal-corneal region, which aligned with findings from hPSC-LSC differentiation experiments.

Conclusions

WM-IF coupled with quantification of fluorescence intensities proved to be a valuable tool for investigating LSC marker expression in both human and porcine tissues ex vivo. Prolonged storage significantly influences the expression of LSC markers, underscoring the importance of fresh human or substitute control tissue when studying limbal stem cell biology.

Corneal neovascularization (CoNV) is the second leading common cause of vision impairment worldwide and is a blinding pathological alteration brought on by ocular trauma, infection, and other factors. There are some limitations in the treatment of CoNV, hence it's critical to look into novel therapeutic targets. The corneal epithelial barrier, which is the initial barrier of the ocular surface, is an important structure that shields the eye from changes in the internal environment or invasion by the external environment. This study sought to collate evidence on the regulation of corneal epithelial barrier injury on the activation of vascular endothelial cells (VECs), basement membrane (BM) degradation, differentiation, migration, and proliferation of VECs, vascular maturation and stability, and other key processes in CoNV, so as to provide a novel concept for CoNV therapy targeting corneal epithelial barrier repair.

Purpose

Ocular surface hydration is critical for eye health and its impairment can lead to dry eye disease. Extracellular calcium-sensing receptor (CaSR) is regulator of ion transport in epithelial cells expressing cystic fibrosis transmembrane conductance regulator (CFTR) Cl⁻ channel. CFTR is also a major ion channel in ocular surface epithelia, however the roles of CaSR in ocular surface are not well studied. This study aims to investigate expression and functional roles of CaSR in ocular surface.

Methods

CaSR immunostaining was performed in mouse and human cornea and conjunctiva. Ocular surface potential difference (OSPD) and tear fluid volume measurements were performed in mice with topically applied cinacalcet (CaSR activator) and NPS-2143 (CaSR inhibitor).

Results

CaSR is expressed in corneal and conjunctival epithelia of mice and humans. Topically administered CaSR activator cinacalcet inhibits cAMP agonist forskolin-induced Cl⁻ secretion and CFTR activity up to 90 %. CaSR inhibitor NPS-2143 stimulates CFTR-mediated Cl⁻ secretion in mouse ocular surface, after which cAMP agonist forskolin had minimal additional secretory effects. Single dose NPS-2143 treatment (as an eye drop) increases tear fluid volume in mice by ∼60 % compared to vehicle treatment. NPS-2143 effect on tear volume lasts at least 8 h after single dose.

Conclusions

CaSR is a key regulator of ocular surface ion transport and CaSR inhibition promotes Cl⁻ and tear secretion in the ocular surface. If they are found to be effective in in dry eye models, CaSR inhibitors (currently in clinical development) can potentially be repurposed as novel prosecretory treatments for dry eye disease.

Filamentary keratitis (FK) is a clinical sign of underlying ocular and systemic conditions. FK can cause significant irritation, tearing, and photophobia in the eye. It is a refractory debilitating condition caused by dry eye that affects the day-to-day activities of patients. The etiopathogenesis of FK is not well known; there are numerous predisposing causes. The condition starts as a sub-epithelial or Bowman's membrane dysfunction and leads to the shedding of epithelial cells that take a strand-like form and attach to the cornea. These strands are surrounded by mucin and continue to elongate to become filaments. The filament formation is further aided by the shearing action caused by eyelid movements. Several management approaches, such as addressing the underlying causes of filamentary keratitis, administering copious lubricants, topical corticosteroids, mucolytic agents, bandage contact lenses, punctal plugs, and mechanical removal of filaments are available. The prognosis is fair, and most cases resolve with occasional recurrences. Traditionally FK has been treated with lubricants, mechanical removal, and bandage contact lenses. The newer treatments are topical immunomodulators especially that treat filamentary keratitis associated with aqueous deficient dry eye. The review describes the treatment as well as pathogenesis.